Psoralen plus long wavelength ultraviolet radiation (UV-A) is being investigated as a model system for clinically relevant photochemical carcinogenesis. Used experimentally for treatment of psoriasis and mycosis fungoides, psoralen plus UV-A has been found to be mutagenic and carcinogenic. We have developed an in vitro assay to measure the effects of UV-A mediated psoralen-DNA binding on human lymphoid cells. Parameters monitored include the rate of DNA synthesis, induction of DNA-psoralen cross-links, induction of sister chromatid exchanges, alterations in the rate of cell proliferation and survival, and in immune reactivity. These studies indicate that the low doses of psoralen plsu UV-A received by patients' leukocytes during the therapy may result directly in decreased DNA synthesis in their circulating lymphoid cells. This system may be exploited to destroy circulating neoplastic cells by irradiation of extracorporeal blood cells during leukophoresis. These studies are aimed at understanding the mechanism of cell damage induced by psoralen plus UV-A so as to control the toxicity to human cells during therapy and to identify individuals with abnormal sensitivity.